Micro-Abstract Using an established international renal cell carcinoma (RCC) database, we retrospectively characterized the use and efficacy of mammalian target of rapamycin (mTOR) inhibitors in ...treatment-naive metastatic RCC (mRCC) patients. Front-line mTOR inhibitors are used in clinical practice mostly in select patients, who have non-clear cell histology, poor prognostic features, or as part of clinical trials.
To describe a single institution experience in delivering concurrent capecitabine and radiation in elderly patients with urothelial cancer.
The records of patients with urothelial carcinoma treated ...with capecitabine and radiation at Wayne State University were reviewed. Capecitabine was administered at a median dose of 1600 mg/m2/day (range, 1200-1800 mg/m2). Concurrent radiation therapy (RT) of 40-45 Gy was delivered to a small pelvic field with a four-field technique, with additional boost to tumor area (total, 54-68.4 Gy).
Fourteen patients who were not candidates for cystectomy or cisplatin-based therapy were treated with capecitabine and concurrent radiation therapy. Median age was 80 years (range, 46-88 years). Five patients had a performance status of 3. Nine patients had localized disease, and 5 patients had advanced disease. The most common overall toxicities were fatigue (43%), diarrhea (Grade 2, 14% and Grade 3, 29%), and dehydration (43%), with no Grade 4 or 5 toxicities. Of 14 patients, 3 (20%) required hospitalization for management of toxicities. Seven patients required dose modification, and the therapy was relatively well tolerated. Clinical complete response was seen in 11 of 13 evaluable patients (77%). At a median follow-up of 10.5 months, only 3 of 11 responders had relapsed.
Concurrent capecitabine and radiation therapy is well-tolerated and demonstrates promising efficacy in urothelial carcinoma, thus offering a tolerable therapeutic option in elderly patients or those with impaired performance status.
Objectives To evaluate the toxicity and efficacy of capecitabine and weekly docetaxel in a phase II clinical trial. Methods Eligibility included metastatic renal cancer with a maximum of 2 prior ...regimens, performance status of 0-2, and adequate renal, hepatic, and bone marrow function. Docetaxel was administered intravenously at a dose of 36 mg/m2 weekly on days 1, 8, and 15 of a 28- day cycle and capecitabine was administered orally at a dose of 1800 mg/m2 from days 5-18. Toxicity was assessed on days 1, 8, and 15 of each cycle, and response was evaluated every 2 cycles. Results Twenty-five patients, 19 white and 6 African American, were enrolled on this phase II trial. The median age was 60 years (range: 39-75 years). Eighteen patients had clear cell histology, 7 had papillary, sarcomatoid, or chromophobe histology. Thirteen had liver/bone metastases and 13 had ≥2 of the Memorial Sloan-Kettering Cancer Center prognostic risk factors. Twelve patients received prior immunotherapy. A total of 93 cycles were administered; median of 3 cycles and range from 0-10 cycles. The therapy was well tolerated. No treatment-related mortality was observed and 2 treatment-related hospitalizations for nausea, diarrhea, and dehydration occurred. Ten patients had stable disease. The median time to progression was 1.7 months and median survival was 11.1 months. Conclusions The combination of capecitabine and docetaxel was well tolerated in metastatic renal cancer. Clinical activity was predominantly noted in non-clear cell histology in which chemotherapy would be worthy of future investigation.
Paclitaxel and docetaxel have emerged in the last two decades as effective antitumor agents in a variety of malignancies. Paclitaxel is a semisynthetic taxane isolated from bark of the Pacific yew ...tree. Docetaxel is a semisynthetic taxane derived from the needles of the European yew (
Taxus baccata). These compounds bind to tubulin, leading to microtubule stabilization, mitotic arrest and, subsequently, cell death. Plasma clearance of paclitaxel exhibits nonlinear kinetics, which results in a disproportionate change in plasma concentration and area under the curve (AUC) with dose alterations. In contrast, docetaxel has a linear disposition over the dose ranges used clinically, so its concentration changes linearly with changes in the dosage. Premedicating with corticosteroids and histamine H
1 and H
2 receptor antagonists is advocated prior to paclitaxel administration; prior to docetaxel administration, premedication with corticosteroids is suggested. The taxanes are metabolized in the liver by the cytochrome P-450 enzymes and are eliminated in the bile. The known metabolites are either inactive or less potent than the parent compounds. The toxic effects associated with paclitaxel therapy are mainly neutropenia, peripheral neuropathy, and, rarely, cardiotoxicity. Docetaxel toxicity produces mainly myelosuppression and a cumulative dose fluid retention syndrome. Paclitaxel demonstrates sequence-dependent interactions with cisplatin, cyclophosphamide, and doxorubicin. Docetaxel has shown increased myelosuppression with preceding ifosfamide in a preliminary study. The future holds increasing indications for taxanes in newer combination regimens; consideration of their pharmacologic characteristics is an important aspect of designing and applying new taxane-based treatment regimens.
Micro-Abstract ProleukinR Observational Study to Evaluate the Treatment Patterns and Clinical Response in Malignancy (PROCLAIMSM ) is the largest observational clinical database of high-dose ...interleukin-2 (HD IL-2)-treated patients in the US. Herein, the survival and outcome for patients with renal cell carcinoma receiving HD IL-2 in sequence with targeted therapy are described. HD IL-2 has an acceptable efficacy and safety profile in current clinical practice and remains a valuable therapy for patients with renal cell carcinoma.
This analysis describes the outcome for patients who received targeted therapy (TT) prior to or following high-dose interleukin-2 (HD IL-2).
Patients with renal cell carcinoma (n = 352) receiving HD ...IL-2 were enrolled in Proleukin
Observational Study to Evaluate the Treatment Patterns and Clinical Response in Malignancy (PROCLAIM
) beginning in 2011. Statistical analyses were performed using datasets as of September 24, 2015.
Overall, there were 4% complete response (CR), 13% partial response (PR), 39% stable disease (SD), and 43% progressive disease (PD) with HD IL-2. The median overall survival (mOS) was not reached in patients with CR, PR, or SD, and was 15.5 months in patients with PD (median follow-up, 21 months). Sixty-one patients had prior TT before HD IL-2 with an overall response rate (ORR) to HD IL-2 of 19% (1 CR, 9 PR) and an mOS of 22.1 months. One hundred forty-nine patients received TT only after HD IL-2 with an mOS of 35.5 months. One hundred forty-two patients had no TT before or after HD IL-2, and mOS was not reached. The mOS was 8.5 months in PD patients who received HD IL-2 without follow-on TT and 29.7 months in PD patients who received follow-on TT after HD IL-2.
HD IL-2 as sole front-line therapy, in the absence of added TT, shows extended clinical benefit (CR, PR, and SD). Patients with PD after HD IL-2 appear to benefit from follow-on TT. Patients who progressed on TT and received follow-on HD IL-2 experienced major clinical benefit. HD IL-2 therapy should be considered in eligible patients.
The efficacy of weekly high-dose paclitaxel in androgen-independent prostate carcinoma and its cytotoxic synergy with estramustine led to the evaluation of a weekly schedule of paclitaxel and ...estramustine in this Phase II trial.
Patients were eligible if they had metastatic prostate adenocarcinoma with objective progression or rising prostate-specific antigen (PSA) levels despite androgen deprivation therapy and antiandrogen withdrawal. Prior radiation and/or one prior chemotherapy regimen was permitted. A Zubrod performance status of 2 or less and adequate bone marrow and hepatic and renal function were required. Estramustine was administered orally at a dose of 280 mg three times daily on days 1 to 3, 8 to 10, and 15 to 17. Paclitaxel (150 mg/m
2) was administered as a 1-hour intravenous infusion on days 2, 9, and 16. Therapy was repeated every 28 days (one cycle).
Twenty-eight patients were enrolled (median age 71.5 years). Fifteen patients had measurable disease (nine nodal and seven visceral) and 13 had bone-only metastases. A total of 116 cycles of therapy were delivered (median 4 cycles per patient, range 1 to 12). Nine patients required dose reduction. The predominant toxicities consisted of grade 3 neuropathy in 6 patients and grade 3 and 4 neutropenia in 4 patients, with one hospitalization for febrile neutropenia. Three patients had thrombotic manifestations: one deep venous thrombosis and two non-Q wave myocardial infarctions. Of the 28 patients, 26 were assessable for response. Of 13 patients with measurable disease, 5 demonstrated a partial response (1 in the liver and 4 in the lymph nodes), and 8 of 13 patients with bone-only metastases had a 50% or greater decrease in PSA level. Three patients had a 90% or greater decline in PSA. The overall PSA response rate was 61.53% (95% confidence interval 38.1% to 74.2%). The median time to progression was 4.64 months, and the median survival was 13 months.
The combination of weekly estramustine and paclitaxel is active in metastatic androgen-independent prostate cancer.
To perform a review of patient and disease characteristics and response and survival outcomes of patients with metastatic androgen-independent prostate cancer. Racial differences in prostate cancer ...have usually been attributed to socioeconomic status, quality of care, comorbidities, and dietary factors. In a clinical trial population, some of these factors, such as access to care and performance status, are likely to be relatively uniform.
The patients included in the review had been registered in clinical trials between 1991 and 2001 at Wayne State University.
Of 145 patients, 90 (62%) were white Americans and 55 (38%) were black Americans, 27% were 70 years or older, and 34% had minimal metastatic disease (axial bony involvement and/or lymph node involvement) and 66% had extensive disease (appendicular skeleton and/or visceral involvement). The chi-square test demonstrated no statistically significant difference by race in the distribution of the patient and disease characteristics. The prostate-specific antigen response rate was 41% in whites and 29% in blacks (
P = 0.12). Log-rank analysis revealed race to be the only statistically significant factor predictive of the time to prostate-specific antigen progression (
P = 0.02, median 4.6 months in whites and 2.3 months in blacks). No statistically significant difference by race was found in overall survival. Poor performance status, extensive disease, elevated alkaline phosphatase and lactate dehydrogenase levels, and a lack of prostate-specific antigen response were statistically significant predictors of worse overall survival.
In patients with androgen-independent metastatic prostate cancer studied in clinical trials, race was an independent predictor of therapeutic outcome. Additional investigation of the biologic and genetic differences underlying this clinical disparity is warranted.
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